PubMed Journals: J Virol
Source: PMID: 15681410
⇦ ⇨ J Virol. 2005 Feb;79(4):2079-86.
Inhibition of Beta interferon induction by
severe acute respiratory syndrome coronavirus
suggests a two-step model for activation
of interferon regulatory factor 3.
Spiegel M(1), Pichlmair A, Martínez-Sobrido
L, Cros J, García-Sastre A, Haller O, Weber
(1) Abteilung Virologie, Institut für Medizinische
Mikrobiologie und Hygiene, Universität Freiburg,
D-79008 Freiburg, Germany.
Severe acute respiratory syndrome (SARS) is
caused by a novel coronavirus termed SARS-CoV.
We and others have previously shown that
the replication of SARS-CoV can be suppressed
by exogenously added interferon (IFN), a
cytokine which is normally synthesized by
cells as a reaction to virus infection.
Here, we demonstrate that SARS-CoV escapes
IFN-mediated growth inhibition by preventing
the induction of IFN-beta. In SARS-CoV-infected
cells, no endogenous IFN-beta transcripts
and no IFN-beta promoter activity were detected.
Nevertheless, the transcription factor
interferon regulatory factor 3 (IRF-3),
which is essential for IFN-beta promoter
activity, was transported from the cytoplasm
to the nucleus early after infection with
SARS-CoV. However, at a later time point
in infection, IRF-3 was again localized
in the cytoplasm. By contrast, IRF-3 remained
in the nucleus of cells infected with the
IFN-inducing control virus Bunyamwera delNSs.
Other signs of IRF-3 activation such as
hyperphosphorylation, homodimer formation,
and recruitment of the coactivator
CREB-binding protein (CBP) were found late
after infection with the control virus but
not with SARS-CoV. Our data suggest that
nuclear transport of IRF-3 is an immediate-early
reaction to virus infection and may precede
its hyperphosphorylation, homodimer formation,
and binding to CBP. In order to escape activation
of the IFN system, SARS-CoV appears to block
a step after the early nuclear transport
PMCID: PMC546554 PMID: 15681410 [Indexed